Department of General Surgery, People's Hospital of Putuo District, Zhoushan, Zhejiang, China.
Medicine (Baltimore). 2023 Feb 22;102(8):e32915. doi: 10.1097/MD.0000000000032915.
Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been hypothesized to have important roles in the etiology of hepatocellular carcinoma (HCC). However, the synergistic effect of circRNA and lncRNA in the pathogenesis of HCC has rarely been studied.
In this study, the Gene Expression Omnibus database was used to get the expression profiles of circRNAs, micro RNAs (miRNAs), lncRNAs, and messenger RNAs (mRNAs) in HCC tissues and normal tissues. The accession numbers for this database are GSE101728, GSE155949, and GSE108724. We found 291 differentially overexpressed lncRNAs and 541 differentially overexpressed mRNA in GSE101728, 30 differentially overexpressed circRNA in GSE155949, and 48 significantly downregulated miRNA in GSE198724. Meanwhile, based on Pearson correlation test, we established lncRNA-mRNA networks. We constructed lncRNA/circRNA-miRNA pairs through Starbase database prediction and identified the common miRNAs. The intersection of co-predicted miRNAs and the 48 significantly low expression miRNAs in GSE198724 were included in the following study. miRDB, Targetscan, miRwalk, and lncRNA-related mRNA jointly determined the miRNA-mRNA portion of the circRNA/lncRNA-miRNA-mRNA co-expression network. And, among 55 differentially expressed mRNA in circRNA/lncRNA-miRNA-mRNA network, CPEB3, EFNB3, FATA4, growth hormone receptor, GSTZ1, KLF8, MFAP4, PAIP2B, PHACTR3, PITPNM3, RPS6KA6, RSPO3, SLITRK6, SMOC1, STEAP4, SYT1, TMEM132E, TSPAN11, and ZFPM2 were intimately related to the prognosis of HCC patients in Kaplan-Meier plotter analysis (P < .05).
We have discovered that the prognosis-related lncRNAs/circRNAs-miRNA-mRNA network plays a significant role in the pathogenesis of HCC. These findings may offer fresh perspectives for further research into the pathogenesis of HCC and the search for novel treatments for HCC.
环状 RNA（circRNAs）和长非编码 RNA（lncRNAs）被认为在肝细胞癌（HCC）的发病机制中具有重要作用。然而，circRNA 和 lncRNA 在 HCC 发病机制中的协同作用很少被研究。
本研究利用基因表达综合数据库获取 HCC 组织和正常组织中 circRNA、微小 RNA（miRNA）、lncRNA 和信使 RNA（mRNA）的表达谱。该数据库的访问号为 GSE101728、GSE155949 和 GSE108724。我们在 GSE101728 中发现 291 个差异过表达的 lncRNA 和 541 个差异过表达的 mRNA，在 GSE155949 中发现 30 个差异过表达的 circRNA，在 GSE198724 中发现 48 个显著下调的 miRNA。同时，基于 Pearson 相关性检验，我们建立了 lncRNA-mRNA 网络。我们通过 Starbase 数据库预测构建了 lncRNA/circRNA-miRNA 对，并鉴定了共同的 miRNA。将共预测的 miRNA 与 GSE198724 中 48 个显著低表达的 miRNA 的交集包含在以下研究中。miRDB、Targetscan、miRwalk 和 lncRNA 相关 mRNA 共同确定了 circRNA/lncRNA-miRNA-mRNA 共表达网络中的 miRNA-mRNA 部分。在 circRNA/lncRNA-miRNA-mRNA 网络中 55 个差异表达的 mRNA 中，CPEB3、EFNB3、FATA4、生长激素受体、GSTZ1、KLF8、MFAP4、PAIP2B、PHACTR3、PITPNM3、RPS6KA6、RSPO3、SLITRK6、SMOC1、STEAP4、SYT1、TMEM132E、TSPAN11 和 ZFPM2 在 Kaplan-Meier 绘图仪分析（P<.05）中与 HCC 患者的预后密切相关。
我们发现预后相关的 lncRNAs/circRNAs-miRNA-mRNA 网络在 HCC 的发病机制中起着重要作用。这些发现可能为进一步研究 HCC 的发病机制和寻找新的 HCC 治疗方法提供新的视角。
